Locations

The HZI is continuously building a network of closely aligned strategic partnerships with universities, research institutions and hospitals. Its primary objective is to create synergies which establish the optimal conditions for an efficient transfer of knowledge from basic research to medical application: HZI Locations.

The Strategy of the HZI

Learn more about how the HZI, with its translational focus, will help to facilitate a faster and more targeted approach when it comes to fighting and preventing existing, emerging or recurring infectious diseases.

Working at the HZI

Around 900 employees in research, administration and infrastructure, and about 220 visiting scientists from 40 different countries are employed at the Helmholtz Centre for Infection Research. To ensure top quality research we need top quality employees. Your creativity and innovative capabilities are the basis for the long-term success of our work. That's why we undertake a great deal to attract the best people to us. Learn more about this.

Feature

Systems BiologyThe goal of systems biology is to describe the dynamic processes of life and of biological systems using mathematical models. In line with the foundation of the new Braunschweig Integrated Centre of Systems Biology (BRICS) we have compiled some background information about systems biology for you: To the systems biology feature.

Sensor of bacteria and viruses on high alert at the site of action

HZI/Oelkers[Improvision Data]..ImageName=Image.TimeStampMicroSeconds=0.TimeStamp=00:00:00,000.ChannelName=.ChannelNo=1.TimepointName=1.TimepointNo=1.ZPlane=1.BlackPoint=0.WhitePoint=255.WhiteColour=255,255,255.TotalChannels=1.TotalTimepoints=1.TotalZPlanes=1.Software=Volocity 6.1.1."Danger!" signals TLR9, the molecular sensor, whenever it recognizes bacterial or viral genetic information, specifically DNA. Instantly, the immune system initiates the process of fighting off the infection. This initial protective mechanism is very fast because it focuses on recognition of basic structural properties – in this case bacterial or viral DNA. Now, researchers at the Helmholtz Centre for Infection Research (HZI) have shown that TLR9 not only quickly recognizes DNA, it also waits, ready for action, right at the site where it will encounter it.

It is through mechanisms like these that we gain valuable time before acquired immunity, the more effective but much slower branch of the immune system, is activated. Together with their German, US, and South Korean colleagues, HZI scientists have examined what the requirements for TLR9 function are in different kinds of immune cells. The researchers have now published their findings in “The Journal of Immunology”, which has ranked this research among the top ten per cent of the scientific journal's total published contributions.

The scientists expect that their insights might be exploited for therapeutic purposes. "In addition to its classic job, TLR9 could potentially help with disease prevention. One option, which is currently under investigation in clinical studies, is adding DNA to vaccines - to switch on TLR9 and thereby activate the immune system more strongly," explains Prof. Melanie Brinkmann, head of HZI's Viral Immune Modulation research group. In other instances it may make sense to inhibit this molecule - as in those cases where it erroneously recognizes the body's own DNA, causing autoimmune diseases. "In order to fully grasp the potential of this and similar molecules, we need to better understand how TLR9 functions in immune cells," explains Brinkmann. The researchers are especially interested in figuring out how the molecule gets from the location within the cell where it is produced into the endolysosomes. It is inside these tiny bubbles that it ultimately encounters the DNA of invading bacteria or viruses.

To trace TLR9's movements within the cell, the researchers developed a murine model, in which mice produced a color-labeled version of the protein. With the help of a microscope, the scientists were able to localize TLR9 inside different immune cells, revealing how it is capable of such a rapid response. Prior to a bacterial or viral infection, the sensor migrates into the endolysosomes to "await" potential intruders. By thus positioning TLR9, the cell ensures a given pathogens' rapid detection.

In order to be fully operational, a portion of the protein must first be cleaved off – this is done by “molecular scissors”, which the researchers identified as well. Both transport into the endolysosomes and cleavage of the protein depend upon the presence of a second protein called UNC93B1. "We thus managed to identify a number of important components that are key to TLR9's ability to recognize bacterial and viral intruders and set off an alarm," says Dr. Margit Oelkers, another HZI scientist involved in the project. Studying TLR9's transport within different immune cell types, the researchers found out that the process actually varies from one cell type to the next. Says Brinkmann: "The results are helping us better understand how TLR9 works. Our findings are critical if we are to exploit the molecule's properties for therapeutic purposes."

Ideally, our immune system will recognize and subsequently eliminate pathogens that enter our bodies. However, many microorganisms and viruses have evolved strategies to evade immune detection. The “Viral Immune Modulation” research group seeks to uncover the different mechanisms that particularly herpes viruses use to perform this feat.